The skin, which is the body's largest organ, is essential to an organism's survival as it forms a physical barrier that helps prevent harmful microorganisms and chemicals from entering the body. As well as resisting harmful elements from entering it, the skin has a role in secreting certain waste products from the body. In addition, the skin is a protective structure for internal organs as it softens potential blows to the body. Also, the skin prevents the loss of body fluids and shields the internal organs from damaging ultraviolet light from the sun.
The skin is between 1.4 to 4.0 mm thick. Generally, the skin is relatively thin in places that are most visible (e.g. thighs, forearms, face etc.) with the thickest areas being areas of the body that are subjected to rubbing or friction such as the palms of the hands and the soles of the feet.
Regardless of the thickness, the skin consists of two distinct layers, the epidermis and the dermis. The epidermis is the outer layer of the skin and is a tough, waterproof, protective layer. The dermis, or inner layer, is thicker than the epidermis and gives the skin its strength and elasticity. The two layers of the skin are anchored to one another by a thin but complex layer of tissue known as the basement membrane which is composed of a series of elaborately interconnecting molecules that serve to hold the skin together. Below the dermis is the subcutaneous layer, the hypodermis, which is a layer of tissue composed of protein fibers and adipose tissue. Although not technically part of the skin, the subcutaneous layer contains glands and other skin structures, as well as sensory receptors involved in the sense of touch.
Although very resilient, skin can be damaged in many ways, and sometimes permanently. The skin begins repair immediately upon injury.
Wound healing, or wound repair, is an intricate process in which the skin (or another organ-tissue) repairs itself after injury. In normal skin, the epidermis (outermost layer) and dermis (inner or deeper layer) exists in steady-state equilibrium, forming a protective barrier against the external environment. Once the protective barrier is broken, the normal (physiologic) process of wound healing is immediately set in motion. The classic model of wound healing is divided into three or four sequential, yet overlapping, phases: (1) hemostasis (not considered a phase by some authors), (2) inflammatory, (3) proliferative and (4) remodeling. Upon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage. Within minutes post-injury, platelets (thrombocytes) aggregate at the injury site to form a fibrin clot. This clot acts to control active bleeding (hemostasis).
In the inflammatory phase, bacteria and debris are phagocytosed and removed, and factors are released that cause the migration and division of cells involved in the proliferative phase.
The proliferative phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction. In angiogenesis, new blood vessels are formed by vascular endothelial cells. In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin. Concurrently, re-epithelialization of the epidermis occurs, in which epithelial cells proliferate and ‘crawl’ atop the wound bed, providing cover for the new tissue.
In contraction, the wound is made smaller by the action of myofibroblasts, which establish a grip on the wound edges and contract themselves using a mechanism similar to that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.
In the maturation and remodeling phase, collagen is remodeled and realigned along tension lines and cells that are no longer needed are removed by apoptosis.
The wound healing or wound repair process occurs frequently with skin since there is a high incidence of injury to the skin. Severe injury due to invasive skin surgery (e.g. ablation of cancerous skin tissue) or accidental collision with an object or burns can involve all layers of the skin (full thickness wounds) in which wound repair may be lengthy and is likely to result in overt scarring. Skin deformities or permanent abnormalities are possible manifestations of deep wound healing and repair. The process of wound healing is fragile and susceptible to interruption or failure leading to the formation of chronic non-healing wounds. Factors which may contribute to this include diabetes, venous or arterial disease, old age, and infection.
A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and degradation plays too large a role.
Chronic wounds may never heal or may take years to do so. These wounds cause patients severe emotional and physical stress as well as creating a significant financial burden on patients and whole healthcare systems. The integrity and appearance of the skin associated with a chronic wound is unsatisfactory with the strength of skin around 50% or less. There is no effective treatment for chronic wound.
When it comes to skin appearance, there is deep emotional stress associated with physical abnormalities of the skin. These abnormalities could be congenital or environmentally triggered (e.g. from severe burns) and visually present as deep pockets or crevices in the face, for example. The approach to repairing and reshaping tissue is limited to skin grafts and poorly performing skin substitutes. However, most of these treatments are suboptimal as they are linked to various deficiencies, such as:
Limited availability of donor tissue;
Grafted dermis does not regenerate, resulting in scars that contract;
Larger donor sites are needed to compensate for graft shrinkage;
Harvested donor sites are painful, itchy and red;
The requirement for the donor skin or the skin substitute to be replaced numerous times during the healing process;
Scaled, rough, dry appearance in skin at the wound site;
Likelihood of tissue rejection;
Stiffness of graft area; and
Overall disappointing functional and cosmetic outcomes.